The Philadelphia chromosome (Ph) negative Myeloproliferative Disorders (MPD) include Polycythemia Vera[unreadable] (PV), Essential Thrombocythemia (ET), and Idiopathic Myelofibrosis (IM). Although typically chronic, subsets[unreadable] of these patients, especially those with IM, have a more aggressive disease course. Complications of these[unreadable] diseases include thrombosis, marrow failure and transformation to acute leukemia. The contributing factors[unreadable] that lead to these complications are not well established. The objectives of Project 6 are to establish a[unreadable] clinical trials working group that can rapidly test hypothesis driven novel therapeutic approaches in Ph- MPD[unreadable] where there is either a general lack of effective therapies (IM) or the "standard of care" is often based on[unreadable] inadequate or conflicting clinical trial data (PV). This infrastructure will permit the conduct of a series of[unreadable] clinical trials to develop biomarkers to predict the development of these complications, and to determine[unreadable] optimal treatment strategies for the Ph negative MPD. In order to accomplish these goals the following[unreadable] specific aims will be pursued:[unreadable] Specific Aim 1: To conduct a phase II trial with SCT and RIC in intermediate/high risk IM patients with an[unreadable] HLA identical allogeneic stem cell donor.[unreadable] Specific Aim 2: To conduct a randomized phase II trial using Simon 2- stage designs to evaluate[unreadable] bortezomib and bevacizumab in the initial phase of this project in IM patients with high risk disease.[unreadable] Specific Aim 3: To conduct a randomized phase II trial in intermediate and high risk PV patients (comparing[unreadable] interferon +/- imatinib mesylate) and to measure biomarkers serially in all patients to determine their value as[unreadable] indicators of therapeutic response and/or risk reduction.[unreadable] Specific Aim 4: To measure biomarkers in all patients enrolled in clinical trials and determine their prognostic[unreadable] value.[unreadable] Specific Aim 5: To provide specimens required for the completion of Projects 1-3 and 5 of the MPD-RC from[unreadable] those patients who are are not participating in treatment protocols described in Specific Aims 1, 2 and 3 of[unreadable] this project. To validate biomarkers in specimens obtained from patients with low risk IM or PV who are[unreadable] receiving treatment with hydroxyurea under a "standard of care" treatment protocol.[unreadable] The completion of these specific aims will result in pivotal information concerning the treatment of high risk[unreadable] Ph- MPD. The study of novel biomarkers will establish unique and simpler means of diagnosis, replacing[unreadable] complicated and expensive schemes currently used in clinical practice.[unreadable]